OVERALL PROJECT SUMMARY Regeneration of damaged and lost tissues is limited in humans and other mammals. However, robust regeneration is the norm for numerous diverse invertebrates and lower vertebrates. COBRE Phase I, Comparative Biology of Tissue Repair, Regeneration and Aging, played a central role in establishing and growing the Kathryn W. Davis Center for Regenerative Biology and Medicine (Davis Center) at the MDI Biological Laboratory (MDIBL) and in dramatically improving the institution?s research environment. The Davis Center was founded on the guiding principle that studying diverse animal models would lead to a detailed and predictive understanding of the cellular and molecular mechanisms of tissue and organ regeneration, and an understanding of why these processes are poorly active in most human tissues and of why they decline with disease and aging. This in turn would lead to a rational foundation for development of regenerative medicine therapies, particularly small molecule drug candidates capable of stimulating tissue regeneration and slowing or reversing aging-induced degenerative changes in patients. COBRE Phase I supported four early-career Project Leaders and one mid-career Project Leader. All five Project Leaders graduated from Phase I with independent grant support. The average time for graduation of the four early-career Project Leaders was 2.8 years. Phase I Project Leaders also achieved multiple other successes including publication of significant peer-reviewed papers, creation of intellectual property, receipt of foundation and R21 grants and significant peer recognition. Other noteworthy successes include further development and patenting of MSI-1436, the only small molecule known to stimulate regeneration of the adult mammalian heart following a heart attack, discovery of two small molecules with potential to reverse chemotherapy-induced peripheral nerve damage, development of new disease models and research tools, and formation of a growing IDeA program/Maine state government partnership that allowed MDIBL to obtain $3M in voter-approved state bond funding to expand research infrastructure. COBRE Phase II will continue to support the growth and development of the Davis Center in order to establish a self-sustaining critical mass of investigators. Three new early-career scientists, Drs. Sam Beck, James Godwin and Jarod Rollins, have been recruited as Phase II Project Leaders. Recruitment of a fourth Davis Center faculty member is underway. Research programs of Phase II Project Leaders are highly synergistic with and bring new scientific expertise to the Davis Center. Essential services and resources will be provided to the Project Leaders and larger scientific community by continuation of the Comparative Functional Genomics Core and Comparative Animal Models Core. COBRE Phase II will greatly enhance the development of the Davis Center and MDIBL, which in turn will contribute to the continued enhancement of the biomedical research environment in Maine.